Substituted imidazo[1, 2-a]-5,6,7,8-tetrahydropyridine-8-ones, method for their production and the use thereof for producing imidazo[1,2-a]pyridines

Abstract

A process for the preparation of imidazo[1,2-a]-5,6,7,8-tetra hydropyridin-8-ones by reaction of γ-butyrolactones with imidazols, novel imidazo[1,2-a]-5,6,7,8-tetrahydropyridin-8-ones, and their use for the preparation of imidazo[1,2-a]pyridines are described.

1. A process for the preparation of imidazo-[1,2a]-5,6,7,8-tetra-hydropyridin-8-ones, of the formula 
       
         
           
           
               
               
           
         
       
       which comprises
 a) reacting a γ-butyrolactone of the formula III 
 
       
         
           
           
               
               
           
         
         with an imidazole of the formula IIa or IIb 
       
       
         
           
           
               
               
           
         
         wherein at least one of R 1  or R 2  is different from hydrogen, and 
         b) isolating the imidazo[1,2a]-5,6,7,8-tetrahydropyridin-8-one, where R1, R2 or every R3 is simply independently selected from the group consisting of hydrogen, unsubstituted, branched or unbranched or cyclic alkyl, substituted or unsubstituted aryl, where the number of substituents R3 can assume a value n from 1 to 3. 
       
     
     
       2. The process as claimed in  claim 1 , wherein the reaction mixture is heated to temperatures from 150° C. to 250° C. 
     
     
       3. A process as claimed in  claim 1 , wherein the γ-butyrolactone is employed in excess. 
     
     
       4. A process as claimed in  claim 1 , wherein the γ-butyrolactone is used as a solvent and during or after the reaction the water of reaction and some or the total amount of the excess γ-butyrolactone is removed. 
     
     
       5. A process as claimed in  claim 1 , wherein R1 and R2 are not hydrogen. 
     
     
       6. A process as claimed in  claim 1 , wherein R1 and R2 are identical. 
     
     
       7. A process as claimed in  claim 1 , wherein R1 and R2 are methyl and R3 is hydrogen. 
     
     
       8. A process for the production of an imidazo[1,2a]pyridine, said process comprising preparing an imidazo[1,2a]-5,6,7,8-tetrahydropyridin-8-one of the formula Ia or Ib by the process of  claim 1 , and further comprising reacting the imidazol of formula Ia or Ib with an aryl- or alkylamine and subsequent oxidative aromatization, or with ammonia, subsequent oxidative aromatization and alkylation or arylation or oxidative aromatization and subsequent alkylation or arylation. 
     
     
       9. The process according to  claim 8 , wherein the imidazo[1,2a]pyridine is described by the formula IV 
       
         
           
           
               
               
           
         
       
       and
 a) where the number of substituents R3 can assume a value n from 1 to 3 and 
 b) A is O or NH, and 
 c) R4 is selected from the group consisting of substituted or unsubstituted, branched or unbranched C 1 –C 6 -alkyl, C 2 –C 6 -alkenyl, C 2 –C 6 -alkynyl, C 3 –C 7 cycloalkyl, C 3 –C 6 -alkadienyl, halo-C 1 –C 6 -alkyl, C 1 –C 6 -alkoxy, C 2 –C 6 -alkenyloxy, C 2 –C 6 -alkynyloxy, C 1 –C 6 -alkyloxy-C 1 –C 6 -alkyl, C 1 –C 6 -alkyloxy-C 2 –C 6 -alkenyl, C 1 –C 6 -alkyloxy-C 2 –C 6 alkynyl, cyano-C 1 –C 6 -alkyl, isocyano-C 1 –C 6 -alkyl, amino-C 1 –C 6 -alkyl, amino-C 2 –C 6 -alkyl, carboxyl, C 1 –C 6 -alkylcarboxyl, substituted or unsubstituted aryl, arylalkyl, heteroaryl and heteroarylalkyl. 
 
     
     
       10. A process for the production of an imidazo[1,2a]pyridine, said process comprising preparing an imidazo[1,2a]-5,6,7,8-tetrahydropyridin-8-one of the formula Ia or Ib by the process of  claim 1 , further comprising reacting an imazdol of formula Ia or Ib with a 2-amino-3-phenylpropionic acid and subsequent oxidation and optionally subsequent hydrogenation to obtain compounds of formula V 
       
         
           
           
               
               
           
         
       
       where
 a) the number of substituents R3 can assume a value n from 1 to 2 and 
 b) R5a and R5b are selected from the group consisting of hydrogen, hydroxyl, C 1 –C 6 -alkoxy, C 1 –C 6 -alkoxy-C 1 –C 6 -alkoxy, C 1 –C 6 -alkylcarbonyloxy, where R5a and R5b can also together be oxygen (oxo group), and 
 c) R6a and R6b are selected from the group consisting of hydrogen, hydroxyl, C 1 –C 6 -alkoxy, C 1 –C 6 -alkoxy-C 1 –C 6 -alkoxy, C 1 –C 6 -alkylcarbonyloxy, where at least one of the radicals R6a or R6b is hydrogen and where R6a and R6b can also together be oxygen (oxo group), and 
 d) R7 is selected from the group consisting of hydrogen, halogen, C 1 –C 6 -alkyl, C 1 –C 6 -alkoxy, C 1 –C 6 -alkoxy-carbonylamino, C 1 –C 6 -alkoxy-C 1 –C 6 -alkoxycarbonylamino or trifluoromethyl, and 
 e) R8 is selected from the group consisting of hydrogen, halogen, C 1 –C 6 -alkyl, C 1 –C 6 -alkoxy.